Chediak-Higashi syndrome

What is Chediak-Higashi syndrome?

Chediak-Higashi syndrome is a childhood disorder that interferes with immune system function. It is also known as Begnez-Cesar syndrome, leukocyte anomaly albinism or defect in natural killer lymphocytes.

It was first described in 1943 by Dr Beguez-Cesar.

Who gets Chediak-Higashi syndrome?

Chediak-Higashi syndrome is rare.

• An estimated 200–500 cases have been reported worldwide.
• The incidence is the same in males and females.
• It affects all races, but researchers suspect its occurrence may be under-reported.

What causes Chediak-Higashi syndrome?

Chediak-Higashi syndrome is an autosomal recessive condition caused by a mutation on the LYST gene. It is often due to parental consanguinity. The LYST gene affects the creation and maintenance of storage granules and causes problems with the transport of a protein across cells.

Chediak Higashi syndrome genetics* 

*Image courtesy Genetics 4 Medics

What are the clinical symptoms of Chediak-Higashi syndrome?

Signs and symptoms begin to affect children with Chediak-Higashi syndrome shortly after birth or by age five at the latest.

• Oculocutaneous albinism, or hypopigmentation of the hair, eyes and skin; hair is described as light in colour with a metallic sheen
• Prolonged bleeding and easy bruising due to platelet abnormalities
• Frequent viral, bacterial and fungal infections
• Photosensitivity
• Nystagmus: abnormal, involuntary eye movements
• Numbness/tingling in the limbs due to peripheral neuropathy
• Poor immunity due to abnormal function and shape of natural killer cells

Onset of Chediak-Higashi syndrome in adult life is associated with milder symptoms. These may include:

• Jaundice
• Skin infections
• Recurrent infections of the sinuses or respiratory tract
• Enlarged lymph glands
• Gum disease (gingivitis)
• Hyperhidrosis and miliaria
• Fever without infection.

Complications of Chediak-Higashi syndrome

The majority of patients (around 80%) will undergo an accelerated phase of Chediak-Higashi syndrome. This phase is marked by the nonmalignant reproduction of white blood cells in multiple body organs. This accelerated phase can be precipitated by the presence of a viral infection, and it is often fatal if it occurs in childhood. This phase is called haemophagocytic lymphohistiocytosis (HLH).

How is Chediak-Higashi syndrome diagnosed?

Diagnosis of Chediak-Higashi syndrome is made by:

• Examination of the white blood cells for the presence of large granules
• Light microscopy of the hair to find pigment clumping.

How is Chediak-Higashi syndrome treated?

Treatment for Chediak-Higashi syndrome may include:

• Cord blood or bone marrow transplant, which is considered the treatment of choice; it is more successful if done before a child reaches the accelerated phase of the disease
• Chemotherapy is needed to put hemophagocytosis (the HLH phase) into remission before a transplant can take place
• Avoidance of exposure to sunlight and sun protective measures

What is the outlook for Chediak-Higashi syndrome?

Without treatment, the outlook for Chediak-Higashi syndrome is poor. Around 50–85% of children with this disorder will enter the accelerated HLH phase. This process with fatal without treatment and most patients will die by the age of 10 years.